Elucidating the role of peripheral monocyte nicotinic acetylcholine receptors and inflammation in cognitive outcomes in older adults
Bibliographic record
Abstract
Abstract Nicotinic acetylcholine receptors (nAChRs) are important regulators of brain and immune function that play critical roles in the neuropathology and progression of Alzheimer’s disease and related dementias (ADRD). However, quantifying nAChRs in the brain remains elusive, and little is known about peripheral measures of nAChR in older adults or their relationship to cognition. Here, we examined associations between nAChR expression and immunoregulatory function in peripheral blood monocytes and cognitive performance among 167 older adults (age 72.3 ± 7.6 years; 71% female). Penalized linear and logistic regression were used to identify nAChR-related features in classical, intermediate, and nonclassical monocytes, as well as immunophenotypes, clinical and sociodemographic factors, associated with cognitive status (Montreal Cognitive Assessment; MoCA). Intermediate monocytes had the highest expression of alpha-7 nAChRs and greater ex vivo inflammatory responses (83.7% TNF-ɑ+ cells) relative to classical (68.4%, d = 1.98, P < 0.001) or nonclassical monocytes (58.9%, d = 3.20, P < 0.001). Participants with mild cognitive impairment (MCI: N = 76) had higher soluble CD14 levels (1777 ± 377 pg/uL) and greater anticholinergic medication burden (ACB; mean = 1.76) than normocognitive participants (NC: N = 91; 1638 ± 352 pg/uL sCD14, t 155 = 2.78, P = 0.006; mean ACB: 1.05, t 143 = 3.13, P = 0.002). Multivariate regression models indicated that stronger nAChR-mediated immunoregulation in intermediate monocytes was associated with higher MoCA scores (beta = 0.13) and 14% lower odds of MCI, as well as lower ACB (beta = − 2.10; 95% CI − 4.14, − 0.61). This study demonstrates that peripheral monocytes exhibit subset-specific differences in nAChR phenotypes in older adults and provides preliminary evidence for their association with cognitive function and a potential mediating role between ACB and cognitive impairment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".